Skip to main content
Erschienen in: Current Obstetrics and Gynecology Reports 2/2020

06.04.2020 | Family Planning (A Burke, Section Editor)

Recent Advances in the Medical Management of Early Pregnancy Loss

verfasst von: Jade M. Shorter, Courtney A. Schreiber, Sarita Sonalkar

Erschienen in: Current Obstetrics and Gynecology Reports | Ausgabe 2/2020

Einloggen, um Zugang zu erhalten

Abstract

Purpose of Review

To provide an update on advances in medical management of early pregnancy loss, including the addition of mifepristone pretreatment to existing regimens.

Recent Findings

The utilization of misoprostol for medical management of early pregnancy loss has been studied extensively and is established as a safe and effective treatment. Two recent randomized controlled trials have demonstrated that the addition of mifepristone pretreatment significantly increases the effectiveness of misoprostol and a large body of data demonstrate the excellent safety profile of mifepristone. However, the Food and Drug Administration Risk Evaluation and Mitigation Strategy restrictions impose a major barrier to mifepristone use.

Summary

The addition of mifepristone to existing misoprostol regimens has significantly improved the effectiveness and patient-centered benefits of medical management of early pregnancy loss. Mifepristone restrictions need to be removed in order to decrease the barriers to women obtaining evidence-based care.
Literatur
1.
Zurück zum Zitat ACOG Practice Bulletin No. 200. Summary: early pregnancy loss. Obstet Gynecol. 2018;132(5):1311–3.CrossRef ACOG Practice Bulletin No. 200. Summary: early pregnancy loss. Obstet Gynecol. 2018;132(5):1311–3.CrossRef
2.
Zurück zum Zitat Hemminki E. Treatment of miscarriage: current practice and rationale. Obstet Gynecol. 1998;91(2):247–53.PubMedCrossRef Hemminki E. Treatment of miscarriage: current practice and rationale. Obstet Gynecol. 1998;91(2):247–53.PubMedCrossRef
3.
Zurück zum Zitat Wang X, Chen C, Wang L, Chen D, Guang W, French J. Conception, early pregnancy loss, and time to clinical pregnancy: a population-based prospective study. Fertil Steril. 2003;79(3):577–84.PubMedCrossRef Wang X, Chen C, Wang L, Chen D, Guang W, French J. Conception, early pregnancy loss, and time to clinical pregnancy: a population-based prospective study. Fertil Steril. 2003;79(3):577–84.PubMedCrossRef
4.
Zurück zum Zitat Warburton D, Fraser FC. Spontaneous abortion risks in man: data from reproductive histories collected in a medical genetics unit. Am J Hum Genet. 1964;16:1–25.PubMedPubMedCentral Warburton D, Fraser FC. Spontaneous abortion risks in man: data from reproductive histories collected in a medical genetics unit. Am J Hum Genet. 1964;16:1–25.PubMedPubMedCentral
5.
Zurück zum Zitat Ventura SJ, Curtin SC, Abma JC, Henshaw SK. Estimated pregnancy rates and rates of pregnancy outcomes for the United States, 1990-2008. Natl Vital Stat Rep. 2012;60(7):1–21.PubMed Ventura SJ, Curtin SC, Abma JC, Henshaw SK. Estimated pregnancy rates and rates of pregnancy outcomes for the United States, 1990-2008. Natl Vital Stat Rep. 2012;60(7):1–21.PubMed
6.
Zurück zum Zitat Trinder J, Brocklehurst P, Porter R, Read M, Vyas S, Smith L. Management of miscarriage: expectant, medical, or surgical? Results of randomised controlled trial (miscarriage treatment (MIST) trial). BMJ. 2006;332(7552):1235–40.PubMedPubMedCentralCrossRef Trinder J, Brocklehurst P, Porter R, Read M, Vyas S, Smith L. Management of miscarriage: expectant, medical, or surgical? Results of randomised controlled trial (miscarriage treatment (MIST) trial). BMJ. 2006;332(7552):1235–40.PubMedPubMedCentralCrossRef
7.
Zurück zum Zitat Henshaw RC, Cooper K, el-Refaey H, Smith NC, Templeton AA. Medical management of miscarriage: non-surgical uterine evacuation of incomplete and inevitable spontaneous abortion. BMJ. 1993;306(6882):894–5.PubMedPubMedCentralCrossRef Henshaw RC, Cooper K, el-Refaey H, Smith NC, Templeton AA. Medical management of miscarriage: non-surgical uterine evacuation of incomplete and inevitable spontaneous abortion. BMJ. 1993;306(6882):894–5.PubMedPubMedCentralCrossRef
8.
Zurück zum Zitat Chung TK, Cheung LP, Leung TY, Haines CJ, Chang AM. Misoprostol in the management of spontaneous abortion. Br J Obstet Gynaecol. 1995;102(10):832–5.PubMedCrossRef Chung TK, Cheung LP, Leung TY, Haines CJ, Chang AM. Misoprostol in the management of spontaneous abortion. Br J Obstet Gynaecol. 1995;102(10):832–5.PubMedCrossRef
9.
Zurück zum Zitat Committee on Practice B-G. The American College of Obstetricians and Gynecologists Practice Bulletin no. 150. Early pregnancy loss. Obstet Gynecol. 2015;125(5):1258–67.CrossRef Committee on Practice B-G. The American College of Obstetricians and Gynecologists Practice Bulletin no. 150. Early pregnancy loss. Obstet Gynecol. 2015;125(5):1258–67.CrossRef
10.
Zurück zum Zitat Chen BA, Creinin MD. Contemporary management of early pregnancy failure. Clin Obstet Gynecol. 2007;50(1):67–88.PubMedCrossRef Chen BA, Creinin MD. Contemporary management of early pregnancy failure. Clin Obstet Gynecol. 2007;50(1):67–88.PubMedCrossRef
11.
Zurück zum Zitat Zhang J, Gilles JM, Barnhart K, Creinin MD, Westhoff C, Frederick MM, et al. A comparison of medical management with misoprostol and surgical management for early pregnancy failure. N Engl J Med. 2005;353(8):761–9.PubMedCrossRef Zhang J, Gilles JM, Barnhart K, Creinin MD, Westhoff C, Frederick MM, et al. A comparison of medical management with misoprostol and surgical management for early pregnancy failure. N Engl J Med. 2005;353(8):761–9.PubMedCrossRef
12.
Zurück zum Zitat Robledo C, Zhang J, Troendle J, Barnhart K, Creinin MD, Westhoff C, et al. Clinical indicators for success of misoprostol treatment after early pregnancy failure. Int J Gynaecol Obstet. 2007;99(1):46–51.PubMedPubMedCentralCrossRef Robledo C, Zhang J, Troendle J, Barnhart K, Creinin MD, Westhoff C, et al. Clinical indicators for success of misoprostol treatment after early pregnancy failure. Int J Gynaecol Obstet. 2007;99(1):46–51.PubMedPubMedCentralCrossRef
13.
Zurück zum Zitat Schreiber CA, Creinin MD, Reeves MF, Harwood BJ. Mifepristone and misoprostol for the treatment of early pregnancy failure: a pilot clinical trial. Contraception. 2006;74(6):458–62.PubMedCrossRef Schreiber CA, Creinin MD, Reeves MF, Harwood BJ. Mifepristone and misoprostol for the treatment of early pregnancy failure: a pilot clinical trial. Contraception. 2006;74(6):458–62.PubMedCrossRef
14.
Zurück zum Zitat Kollitz KM, Meyn LA, Lohr PA, Creinin MD. Mifepristone and misoprostol for early pregnancy failure: a cohort analysis. Am J Obstet Gynecol. 2011;204(5):386 e1–6.CrossRef Kollitz KM, Meyn LA, Lohr PA, Creinin MD. Mifepristone and misoprostol for early pregnancy failure: a cohort analysis. Am J Obstet Gynecol. 2011;204(5):386 e1–6.CrossRef
15.
Zurück zum Zitat Neilson JP, Hickey M, Vazquez J. Medical treatment for early fetal death (less than 24 weeks). Cochrane Database Syst Rev. 2006;3:CD002253. Neilson JP, Hickey M, Vazquez J. Medical treatment for early fetal death (less than 24 weeks). Cochrane Database Syst Rev. 2006;3:CD002253.
16.
Zurück zum Zitat Neilson JP, Gyte GM, Hickey M, Vazquez JC, Dou L. Medical treatments for incomplete miscarriage. Cochrane Database Syst Rev. 2013;3:CD007223. Neilson JP, Gyte GM, Hickey M, Vazquez JC, Dou L. Medical treatments for incomplete miscarriage. Cochrane Database Syst Rev. 2013;3:CD007223.
17.
Zurück zum Zitat • Lemmers M, Verschoor MA, Kim BV, Hickey M, Vazquez JC, Mol BWJ, et al. Medical treatment for early fetal death (less than 24 weeks). Cochrane Database Syst Rev. 2019;6:CD002253 This systematic review reported similar effectiveness for various routes of misoprostol administration.PubMed • Lemmers M, Verschoor MA, Kim BV, Hickey M, Vazquez JC, Mol BWJ, et al. Medical treatment for early fetal death (less than 24 weeks). Cochrane Database Syst Rev. 2019;6:CD002253 This systematic review reported similar effectiveness for various routes of misoprostol administration.PubMed
18.
Zurück zum Zitat Petrou S, McIntosh E. Women's preferences for attributes of first-trimester miscarriage management: a stated preference discrete-choice experiment. Value Health. 2009;12(4):551–9.PubMedCrossRef Petrou S, McIntosh E. Women's preferences for attributes of first-trimester miscarriage management: a stated preference discrete-choice experiment. Value Health. 2009;12(4):551–9.PubMedCrossRef
19.
Zurück zum Zitat Creinin MD, Schwartz JL, Guido RS, Pymar HC. Early pregnancy failure--current management concepts. Obstet Gynecol Surv. 2001;56(2):105–13.PubMedCrossRef Creinin MD, Schwartz JL, Guido RS, Pymar HC. Early pregnancy failure--current management concepts. Obstet Gynecol Surv. 2001;56(2):105–13.PubMedCrossRef
20.
Zurück zum Zitat • Al Wattar BH, Murugesu N, Tobias A, Zamora J, Khan KS. Management of first-trimester miscarriage: a systematic review and network meta-analysis. Hum Reprod Update. 2019;25(3):362–74 This systematic review and meta-analysis concludes that mifepristone may improve the efffectiveness of existing misoprostol regimens. They call for further researh to help improve inconsistencies between current studies.CrossRef • Al Wattar BH, Murugesu N, Tobias A, Zamora J, Khan KS. Management of first-trimester miscarriage: a systematic review and network meta-analysis. Hum Reprod Update. 2019;25(3):362–74 This systematic review and meta-analysis concludes that mifepristone may improve the efffectiveness of existing misoprostol regimens. They call for further researh to help improve inconsistencies between current studies.CrossRef
21.
Zurück zum Zitat Gemzell-Danielsson K, Bygdeman M, Aronsson A. Studies on uterine contractility following mifepristone and various routes of misoprostol. Contraception. 2006;74(1):31–5.PubMedCrossRef Gemzell-Danielsson K, Bygdeman M, Aronsson A. Studies on uterine contractility following mifepristone and various routes of misoprostol. Contraception. 2006;74(1):31–5.PubMedCrossRef
22.
Zurück zum Zitat Fiala C, Gemzel-Danielsson K. Review of medical abortion using mifepristone in combination with a prostaglandin analogue. Contraception. 2006;74(1):66–86.PubMedCrossRef Fiala C, Gemzel-Danielsson K. Review of medical abortion using mifepristone in combination with a prostaglandin analogue. Contraception. 2006;74(1):66–86.PubMedCrossRef
23.
Zurück zum Zitat Baulieu EE. The steroid hormone antagonist RU486. Mechanism at the cellular level and clinical applications. Endocrinol Metab Clin N Am. 1991;20(4):873–91.CrossRef Baulieu EE. The steroid hormone antagonist RU486. Mechanism at the cellular level and clinical applications. Endocrinol Metab Clin N Am. 1991;20(4):873–91.CrossRef
24.
25.
Zurück zum Zitat Schreiber CA, Creinin MD, Harwood B, Murthy AS. A pilot study of mifepristone and misoprostol administered at the same time for abortion in women with gestation from 50 to 63 days. Contraception. 2005;71(6):447–50.PubMedCrossRef Schreiber CA, Creinin MD, Harwood B, Murthy AS. A pilot study of mifepristone and misoprostol administered at the same time for abortion in women with gestation from 50 to 63 days. Contraception. 2005;71(6):447–50.PubMedCrossRef
26.
Zurück zum Zitat Duan H, Wang NG. Effects of tyrosine alone and tyrosine in combination with RU486 on early pregnancy in mice and the mechanism of action. Yao Xue Xue Bao. 1997;32(8):583–5.PubMed Duan H, Wang NG. Effects of tyrosine alone and tyrosine in combination with RU486 on early pregnancy in mice and the mechanism of action. Yao Xue Xue Bao. 1997;32(8):583–5.PubMed
27.
Zurück zum Zitat Cheng L, Kelly RW, Thong KJ, Hume R, Baird DT. The effect of mifepristone (RU486) on the immunohistochemical distribution of prostaglandin E and its metabolite in decidual and chorionic tissue in early pregnancy. J Clin Endocrinol Metab. 1993;77(3):873–7.PubMed Cheng L, Kelly RW, Thong KJ, Hume R, Baird DT. The effect of mifepristone (RU486) on the immunohistochemical distribution of prostaglandin E and its metabolite in decidual and chorionic tissue in early pregnancy. J Clin Endocrinol Metab. 1993;77(3):873–7.PubMed
28.
Zurück zum Zitat Creinin MD, Fox MC, Teal S, Chen A, Schaff EA, Meyn LA, et al. A randomized comparison of misoprostol 6 to 8 hours versus 24 hours after mifepristone for abortion. Obstet Gynecol. 2004;103(5 Pt 1):851–9.PubMedCrossRef Creinin MD, Fox MC, Teal S, Chen A, Schaff EA, Meyn LA, et al. A randomized comparison of misoprostol 6 to 8 hours versus 24 hours after mifepristone for abortion. Obstet Gynecol. 2004;103(5 Pt 1):851–9.PubMedCrossRef
29.
Zurück zum Zitat Creinin MD, Schreiber CA, Bednarek P, Lintu H, Wagner MS, Meyn LA, et al. Mifepristone and misoprostol administered simultaneously versus 24 hours apart for abortion: a randomized controlled trial. Obstet Gynecol. 2007;109(4):885–94.PubMedCrossRef Creinin MD, Schreiber CA, Bednarek P, Lintu H, Wagner MS, Meyn LA, et al. Mifepristone and misoprostol administered simultaneously versus 24 hours apart for abortion: a randomized controlled trial. Obstet Gynecol. 2007;109(4):885–94.PubMedCrossRef
30.
31.
Zurück zum Zitat Schaff EA, Fielding SL, Westhoff C, Ellertson C, Eisinger SH, Stadalius LS, et al. Vaginal misoprostol administered 1, 2, or 3 days after mifepristone for early medical abortion: a randomized trial. JAMA. 2000;284(15):1948–53.PubMedCrossRef Schaff EA, Fielding SL, Westhoff C, Ellertson C, Eisinger SH, Stadalius LS, et al. Vaginal misoprostol administered 1, 2, or 3 days after mifepristone for early medical abortion: a randomized trial. JAMA. 2000;284(15):1948–53.PubMedCrossRef
32.
Zurück zum Zitat van den Berg J, Gordon BB, Snijders MP, Vandenbussche FP, Coppus SF. The added value of mifepristone to non-surgical treatment regimens for uterine evacuation in case of early pregnancy failure: a systematic review of the literature. Eur J Obstet Gynecol Reprod Biol. 2015;195:18–26.PubMedCrossRef van den Berg J, Gordon BB, Snijders MP, Vandenbussche FP, Coppus SF. The added value of mifepristone to non-surgical treatment regimens for uterine evacuation in case of early pregnancy failure: a systematic review of the literature. Eur J Obstet Gynecol Reprod Biol. 2015;195:18–26.PubMedCrossRef
33.
Zurück zum Zitat •• Schreiber CA, Creinin MD, Atrio J, Sonalkar S, Ratcliffe SJ, Barnhart KT. Mifepristone pretreatment for the medical management of early pregnancy loss. N Engl J Med. 2018;378(23):2161–70 This randomized controlled trial demonstrated signifcantly increased rates of complete uterine evacuation and decreased rates of uterine aspiration for the addition of mifepristone to misoprostol.PubMedPubMedCentralCrossRef •• Schreiber CA, Creinin MD, Atrio J, Sonalkar S, Ratcliffe SJ, Barnhart KT. Mifepristone pretreatment for the medical management of early pregnancy loss. N Engl J Med. 2018;378(23):2161–70 This randomized controlled trial demonstrated signifcantly increased rates of complete uterine evacuation and decreased rates of uterine aspiration for the addition of mifepristone to misoprostol.PubMedPubMedCentralCrossRef
34.
Zurück zum Zitat •• Sinha P, Suneja A, Guleria K, Aggarwal R, Vaid NB. Comparison of mifepristone followed by misoprostol with misoprostol alone for treatment of early pregnancy failure: a randomized double-blind placebo-controlled trial. J Obstet Gynaecol India. 2018;68(1):39–44 This randomized controlled trial showed that mifepristone pretreatment to misoprostol significantly improves the efficay of misoprostol alone.PubMedCrossRef •• Sinha P, Suneja A, Guleria K, Aggarwal R, Vaid NB. Comparison of mifepristone followed by misoprostol with misoprostol alone for treatment of early pregnancy failure: a randomized double-blind placebo-controlled trial. J Obstet Gynaecol India. 2018;68(1):39–44 This randomized controlled trial showed that mifepristone pretreatment to misoprostol significantly improves the efficay of misoprostol alone.PubMedCrossRef
35.
Zurück zum Zitat Rausch M, Lorch S, Chung K, Frederick M, Zhang J, Barnhart K. A cost-effectiveness analysis of surgical versus medical management of early pregnancy loss. Fertil Steril. 2012;97(2):355–60.PubMedCrossRef Rausch M, Lorch S, Chung K, Frederick M, Zhang J, Barnhart K. A cost-effectiveness analysis of surgical versus medical management of early pregnancy loss. Fertil Steril. 2012;97(2):355–60.PubMedCrossRef
36.
Zurück zum Zitat Dalton VK, Liang A, Hutton DW, Zochowski MK, Fendrick AM. Beyond usual care: the economic consequences of expanding treatment options in early pregnancy loss. Am J Obstet Gynecol. 2015;212(2):177 e1–6.CrossRef Dalton VK, Liang A, Hutton DW, Zochowski MK, Fendrick AM. Beyond usual care: the economic consequences of expanding treatment options in early pregnancy loss. Am J Obstet Gynecol. 2015;212(2):177 e1–6.CrossRef
37.
Zurück zum Zitat Nagendra D, Schreiber CA, Koelper N, Sonalkar S, Loza-Avalos S, Harvie H. Cost effectiveness of mifepristone pretreatment for the medical management of nonviable early pregnancy [09OP]. Obstet Gynecol. 2019;133:6.CrossRef Nagendra D, Schreiber CA, Koelper N, Sonalkar S, Loza-Avalos S, Harvie H. Cost effectiveness of mifepristone pretreatment for the medical management of nonviable early pregnancy [09OP]. Obstet Gynecol. 2019;133:6.CrossRef
38.
Zurück zum Zitat Westhoff CL. A better medical regimen for the management of miscarriage. N Engl J Med. 2018;378(23):2232–3.PubMedCrossRef Westhoff CL. A better medical regimen for the management of miscarriage. N Engl J Med. 2018;378(23):2232–3.PubMedCrossRef
39.
Zurück zum Zitat Kulier R, Kapp N, Gulmezoglu AM, Hofmeyr GJ, Cheng L, Campana A. Medical methods for first trimester abortion. Cochrane Database Syst Rev. 2011;11:CD002855. Kulier R, Kapp N, Gulmezoglu AM, Hofmeyr GJ, Cheng L, Campana A. Medical methods for first trimester abortion. Cochrane Database Syst Rev. 2011;11:CD002855.
40.
Zurück zum Zitat American College of O, Gynecologists. Practice bulletin no. 143: medical management of first-trimester abortion. Obstet Gynecol. 2014;123(3):676–92.CrossRef American College of O, Gynecologists. Practice bulletin no. 143: medical management of first-trimester abortion. Obstet Gynecol. 2014;123(3):676–92.CrossRef
41.
Zurück zum Zitat Henney JE, Gayle HD. Time to reevaluate U.S. mifepristone restrictions. N Engl J Med. 2019;381(7):597–8.PubMedCrossRef Henney JE, Gayle HD. Time to reevaluate U.S. mifepristone restrictions. N Engl J Med. 2019;381(7):597–8.PubMedCrossRef
42.
Zurück zum Zitat Mifeprex RSG, Raymond EG, Blanchard K, Blumenthal PD, Cleland K, Foster AM, et al. Sixteen years of overregulation: time to unburden Mifeprex. N Engl J Med. 2017;376(8):790–4.CrossRef Mifeprex RSG, Raymond EG, Blanchard K, Blumenthal PD, Cleland K, Foster AM, et al. Sixteen years of overregulation: time to unburden Mifeprex. N Engl J Med. 2017;376(8):790–4.CrossRef
43.
Zurück zum Zitat Cleland K, Smith N. Aligning mifepristone regulation with evidence: driving policy change using 15 years of excellent safety data. Contraception. 2015;92(3):179–81.PubMedCrossRef Cleland K, Smith N. Aligning mifepristone regulation with evidence: driving policy change using 15 years of excellent safety data. Contraception. 2015;92(3):179–81.PubMedCrossRef
44.
Zurück zum Zitat Pymar HC, Creinin MD, Schwartz JL. Mifepristone followed on the same day by vaginal misoprostol for early abortion. Contraception. 2001;64(2):87–92.PubMedCrossRef Pymar HC, Creinin MD, Schwartz JL. Mifepristone followed on the same day by vaginal misoprostol for early abortion. Contraception. 2001;64(2):87–92.PubMedCrossRef
45.
Zurück zum Zitat Rossi B, Creinin MD, Meyn LA. Ability of the clinician and patient to predict the outcome of mifepristone and misoprostol medical abortion. Contraception. 2004;70(4):313–7.PubMedCrossRef Rossi B, Creinin MD, Meyn LA. Ability of the clinician and patient to predict the outcome of mifepristone and misoprostol medical abortion. Contraception. 2004;70(4):313–7.PubMedCrossRef
Metadaten
Titel
Recent Advances in the Medical Management of Early Pregnancy Loss
verfasst von
Jade M. Shorter
Courtney A. Schreiber
Sarita Sonalkar
Publikationsdatum
06.04.2020
Verlag
Springer US
Erschienen in
Current Obstetrics and Gynecology Reports / Ausgabe 2/2020
Elektronische ISSN: 2161-3303
DOI
https://doi.org/10.1007/s13669-020-00282-0

Weitere Artikel der Ausgabe 2/2020

Current Obstetrics and Gynecology Reports 2/2020 Zur Ausgabe

Current Approaches to Managing Menopause (I Alexander, Section Editor)

Treatment of Midlife Women with Chronic Low Back Pain—Opioids Are a Last-Resort Option

Family Planning (A Burke, Section Editor)

Telemedicine for Medication Abortion: The Time Is Now

Update Gynäkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert – ganz bequem per eMail.